Emerging applications of nanotechnology for the diagnosis and management of vulnerable atherosclerotic plaques

Changes in mechanical properties of the vascular wall as a result of pathological vascular remodeling. (a) Ex vivo stress–strain curves of porcine plaque‐laden versus healthy vascular tissue. All samples were taken from the left anterior descending coronary artery in juvenile pigs, with atherosclerosis induced via standard balloon angioplasty injury. Control samples were obtained from pigs without induced injury. (Reprinted with permission from Ref 24. Copyright 2003 ASME Publications.) (b) Schematic of changes in layer‐by‐layer stiffness during progression of pathological vascular remodeling. Pathological changes that decrease the lumen of a remodeling artery include intimal thickening and constrictive geometric remodeling of the wall, leading to a significant increase in the stiffness of inner layer, while vessel wall rupture that is resulted from artery expansion to increase the lumen for restoration of proper blood flow leads to decreased stiffness of middle and outer layers.

Multimodality imaging of atherosclerosis using nanocrystals encapsulated in high density lipoprotein. T1‐weighted MR images of the aorta of apoE KO mice pre‐ (a and b) and 24 h postinjection (d and e) with Au‐HDL or QD‐HDL. Arrows indicate areas enhanced in the post images. (c and f) T2*‐weighted images of an apoE KO mouse pre‐ and 24 h postinjection with FeO‐HDL. (g–i) Confocal microscopy images of aortic sections of mice injected with nanocrystal HDL. Red is nanocrystal HDL, macrophages are green, and nuclei are blue. Yellow indicates colocalization of nanocrystal HDL with macrophages and is indicated by arrowheads. (j) Fluorescence image of aortas of mice injected with QD‐HDL, QDPEG, and saline. (k) Ex vivo sagittal CT images of the aortas of mice injected with Au‐HDL, Au‐PEG, and saline. (Reprinted with permission from Ref 95. Copyright 2008 American Chemical Society)

Dual‐ligand, protease‐activatable quantum dots for imaging applications. In ‘Proximity Activated Targeting’ (PAT) the targeting ligand (blue) is initially concealed (a) until proteolytic activity through tumor‐secreted MMPs (purple) cleaves a peptide bridge (green) within long chain PEGs. Subsequent diffusion of the MMP and cleavage fragments (c) reveals the ligand‐targeted construct only in the proximity of the tumor (d).

Nanoshell immunoassay. (a) In concept, the nanoshell immunoassay is designed to enable rapid and accurate analyte concentration measurements in whole blood, while minimizing dependency on long sample handling and instrumentation typified by standard immunoassays.166 (b) Absorbance spectra of nanoshells prior to versus 30 min after analyte addition. Peak absorbance is estimated at 725 nm. A decrease in material extinction coefficient is observed as a result of clustering of the nanoshells.

Bovine aortic endothelial cell adhesion and function on nanotextured versus conventional MP35N surfaces. Actin staining on a control dish (plastic), non‐nanotextured and nanotextured MP35N surfaces. The presence of peri‐junctional cortical bands of filamentous actin are clearly visible (arrows) on both the control and textured surfaces, but are not as pronounced on the nontextured surface, showing multiple layers of possibly aggregated cells. (Reprinted with permission from Ref 242. Copyright 2008 Elsevier)